Skip to main content
SpringerLink
Log in

Impact of Subarachnoid Hemorrhage on Local and Global Calcium Signaling in Cerebral Artery Myocytes

  • Conference paper
Early Brain Injury or Cerebral Vasospasm

Part of the book series: Acta Neurochirurgica Supplements ((NEUROCHIRURGICA,volume 110/1))

Abstract

Background: Ca2+ signaling mechanisms are crucial for proper regulation of vascular smooth muscle contractility and vessel diameter. In cerebral artery myocytes, a rise in global cytosolic Ca2+ concentration ([Ca2+]i) causes contraction while an increase in local Ca2+ release events from the sarcoplasmic reticulum (Ca2+ sparks) leads to increased activity of large-conductance Ca2+-activated (BK) K+ channels, hyperpolarization and relaxation. Here, we examined the impact of SAH on Ca2+ spark activity and [Ca2+]i in cerebral artery myocytes following SAH. Methods: A rabbit double injection SAH model was used in this study. Five days after the initial intracisternal injection of whole blood, small diameter cerebral arteries were dissected from the brain for study. For simultaneous measurement of arterial wall [Ca2+]i and diameter, vessels were cannulated and loaded with the ratiometric Ca2+ indicator fura-2. For measurement of Ca2+ sparks, individual myocytes were enzymatically isolated from cerebral arteries and loaded with the Ca2+ indicator fluo-4. Sparks were visualized using laser scanning confocal microscopy. Results: Arterial wall [Ca2+]i was significantly elevated and greater levels of myogenic tone developed in arteries isolated from SAH animals compared with arteries isolated from healthy animals. The L-type voltage-dependent Ca2+ channel (VDCC) blocker nifedipine attenuated increases in [Ca2+]i and tone in both groups suggesting increased VDCC activity following SAH. Membrane potential measurement using intracellular microelectrodes revealed significant depolarization of vascular smooth muscle following SAH. Further, myocytes from SAH animals exhibited significantly reduced Ca2+ spark frequency (~50%). Conclusions: Our findings suggest decreased Ca2+ spark frequency leads to reduced BK channel activity in cerebral artery myocytes following SAH. This results in membrane potential depolarization, increased VDCC activity, elevated [Ca2+]i and decreased vessel diameter. We propose this mechanism of enhanced cerebral artery myocyte contractility may contribute to decreased cerebral blood flow and development of neurological deficits in SAH patients.

M. Koide and M. Nystoriak contributed equally to this work.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Clapham DE. Calcium signaling. Cell 1995;80:259–68.

    Article  PubMed  CAS  Google Scholar 

  2. Hai CM, Murphy RA. Ca2+, crossbridge phosphorylation, and contraction. Annu Rev Physiol. 1989;51:285–98.

    Article  PubMed  CAS  Google Scholar 

  3. Knot HJ, Nelson MT. Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure. J Physiol. 1998;508(Pt 1):199–209.

    PubMed  CAS  Google Scholar 

  4. Nelson MT, Cheng H, Rubart M, Santana LF, Bonev AD, Knot HJ, et al. Relaxation of arterial smooth muscle by calcium sparks. Science 1995;270:633–37.

    Article  PubMed  CAS  Google Scholar 

  5. Wellman GC, Nelson MT Signaling between SR and plasmalemma in smooth muscle: sparks and the activation of Ca2+-senstive ion channels. Cell Calcium. 2003;34:211–29.

    Article  PubMed  CAS  Google Scholar 

  6. Wellman GC Ion channels and calcium signaling in cerebral arteries following subarachnoid hemorrhage. Neurol Res. 2006;28:690–702.

    Article  PubMed  CAS  Google Scholar 

  7. Ishiguro M, Puryear CB, Bisson E, Saundry CM, Nathan DJ, Russell SR, et al. Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage. Am J Physiol Heart Circ Physiol. 2002;283:H2217–225.

    PubMed  CAS  Google Scholar 

  8. Ishiguro M, Wellman TL, Honda A, Russell SR, Tranmer BI, Wellman GC. Emergence of a R-type Ca2+ channel (CaV 2.3) contributes to cerebral artery constriction after subarachnoid hemorrhage. Circ Res. 2005;96:419–26.

    Article  PubMed  CAS  Google Scholar 

  9. Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985;260:3440–50.

    PubMed  CAS  Google Scholar 

  10. Wellman GC, Bonev AD, Nelson MT, Brayden JE. Gender differences in coronary artery diameter involve estrogen, nitric oxide, and Ca2+-dependent K+ channels. Circ Res. 1996;79:1024–30.

    Article  PubMed  CAS  Google Scholar 

  11. Wellman GC, Nathan DJ, Saundry CM, Perez G, Bonev AD, Penar PL, Tranmer BI, Nelson MT. Ca2+ sparks and their function in human cerebral arteries. Stroke 2002;33:802–08.

    Article  PubMed  CAS  Google Scholar 

  12. Perez GJ, Bonev AD, Patlak JB, Nelson MT. Functional coupling of ryanodine receptors to KCa channels in smooth muscle cells from rat cerebral arteries. J Gen Physiol. 1999;113:229–38.

    Article  PubMed  CAS  Google Scholar 

  13. Nystoriak MA, Murakami K, Penar PL, Wellman GC. Ca(v)1.2 splice variant with exon 9* is critical for regulation of cerebral artery diameter. Am J Physiol Heart Circ Physiol. 2009;297:H1820–28.

    Article  PubMed  CAS  Google Scholar 

  14. Bederson JB, Connolly ES, Jr., Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2009;40:994–1025.

    Article  PubMed  Google Scholar 

  15. Hansen-Schwartz J, Vajkoczy P, Macdonald RL, Pluta RM, Zhang JH. Cerebral vasospasm: looking beyond vasoconstriction. Trends Pharmacol Sci. 2007;28:252–56.

    Article  PubMed  CAS  Google Scholar 

  16. Pluta RM, Hansen-Schwartz J, Dreier J, Vajkoczy P, Macdonald RL, Nishizawa S, et al. Cerebral vasospasm following subarachnoid hemorrhage: time for a new world of thought. Neurol Res. 2009;31:151–8.

    Article  PubMed  CAS  Google Scholar 

  17. Lee KR, Hoff JT. Intracranial pressure. In: Youmans JR, editor. Neurological Surgery. Philadelphia, PA: W. B. Saunders Co.; 1996. p. 491–518.

    Google Scholar 

  18. Nelson MT, Patlak JB, Worley JF, Standen NB. Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am J Physiol. 1990;259:C3–18.

    PubMed  CAS  Google Scholar 

  19. Ohkuma H, Ogane K, Tanaka M, Suzuki S. Assessment of cerebral microcirculatory changes during cerebral vasospasm by analyzing cerebral circulation time on DSA images. Acta Neurochir Suppl. 2001;77:127–30.

    PubMed  CAS  Google Scholar 

  20. Takeuchi H, Handa Y, Kobayashi H, Kawano H, Hayashi M. Impairment of cerebral autoregulation during the development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates. Neurosurgery 1991;28:41–8.

    Article  PubMed  CAS  Google Scholar 

  21. Harder DR, Dernbach P, Waters A. Possible cellular mechanism for cerebral vasospasm after experimental subarachnoid hemorrhage in the dog. J Clin Invest. 1987;80:875–80.

    Article  PubMed  CAS  Google Scholar 

  22. Ishiguro M, Morielli AD, Zvarova K, Tranmer BI, Penar PL, Wellman GC Oxyhemoglobin-induced suppression of voltage-dependent K+ channels in cerebral arteries by enhanced tyrosine kinase activity. Circ Res. 2006;99:1252–60.

    Article  PubMed  CAS  Google Scholar 

  23. Jahromi BS, Aihara Y, Ai J, Zhang ZD, Nikitina E, Macdonald RL. Voltage-gated K+ channel dysfunction in myocytes from a dog model of subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2008;28:797–811.

    Article  PubMed  CAS  Google Scholar 

  24. Koide M, Penar PL, Tranmer BI, Wellman GC. Heparin-binding EGF-like growth factor mediates oxyhemoglobin-induced suppression of voltage-dependent potassium channels in rabbit cerebral artery myocytes. Am J Physiol Heart Circ Physiol. 2007;293:H1750–59.

    Article  PubMed  CAS  Google Scholar 

  25. Quan L, Sobey CG. Selective effects of subarachnoid hemorrhage on cerebral vascular responses to 4-aminopyridine in rats. Stroke 2000;31:2460–65.

    Article  PubMed  CAS  Google Scholar 

  26. Sobey CG, Faraci FM. Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin Exp Pharmacol Physiol. 1998;25:867–76.

    Article  PubMed  CAS  Google Scholar 

  27. Jahromi BS, Aihara Y, Ai J, Zhang ZD, Weyer G, Nikitina E, et al. Preserved BK channel function in vasospastic myocytes from a dog model of subarachnoid hemorrhage. J Vasc Res. 2008;45:402–15.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Totman Medical Research Trust Fund, the Peter Martin Brain Aneurysm Endowment, the NIH (NIHLBI, R01 HL078983 and NCRR, P20 RR16435) and the American Heart Association (0725837T, 0815736D). The authors wish to thank to Ms. Sheila Russell for her assistance with this study. The authors would also like to acknowledge the University of Vermont Neuroscience COBRE molecular biology and imaging core facilities.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Vermont College of Medicine, Burlington, VT, 05405-0068, USA

    Masayo Koide, Matthew A. Nystoriak, Joseph E. Brayden & George C. Wellman

Authors
  1. Masayo Koide
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew A. Nystoriak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph E. Brayden
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George C. Wellman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George C. Wellman .

Editor information

Editors and Affiliations

  1. Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing, 400038, China

    H.-J. Steiger  & Hua Feng  & 

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

    Ying Mao

  3. Departments of Physiology and Neurosurgery, Loma Linda University School of Medicine, Risley Hall, Room 223, 92354, Loma Linda, California, USA

    John H. Zhang

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag/Wien

About this paper

Cite this paper

Koide, M., Nystoriak, M.A., Brayden, J.E., Wellman, G.C. (2011). Impact of Subarachnoid Hemorrhage on Local and Global Calcium Signaling in Cerebral Artery Myocytes. In: Feng, H., Mao, Y., Zhang, J.H. (eds) Early Brain Injury or Cerebral Vasospasm. Acta Neurochirurgica Supplements, vol 110/1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0353-1_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-0353-1_25

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-0352-4

  • Online ISBN: 978-3-7091-0353-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation